tbuckley/cabot-search huggingface dataset:
PB2228: WHAT IS THE UTILITY OF THE MYSEC-PM ON SECONDARY MYELOFIBROSIS RISK STRATIFICATION IN A REAL LIFE SETTING?
Authors: Pedro Moura, Bárbara Marques, Carolina Afonso, Rita Gomes, Sara Duarte, José Pedro Carda, Catarina Geraldes Santos, Raquel Guilherme
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: The Myelofibrosis Secondary to PV and ET – Prognostic Model (MYSEC-PM) was validated in 2018 in order to predict overall survival (OS) and define the therapeutic approach in patients with Myelofibrosis secondary to Polycythemia Vera and Essential Thrombocythemia (ET). Aims: This study aims to evaluate the applicability of the MYSEC-PM in a clinical practice setting and compare its efficacy with the Dynamic International Prognostic Scoring System (DIPSS). Methods: Single-center and retrospective study, with patients diagnosed with Secondary Myelofibrosis (SMF) between 2012 and 2022. The cohort was characterized and prognostic scores were applied at the time of the initial diagnosis. The OS of each of the MYSEC-PM risk groups was analyzed and compared to the DIPSS risk groups by the Kaplan-Meier method, log-rank test. Results: There was a total of 39 patients included, median age 66 (47-82) years, 71.8% (n=28) were males. The majority (56.4%; n=22) had an initial diagnosis of ET. Median time to SMF progression was 66.9 (21.9-289.7) months. The most common drive mutation was JAK2V617F (87.2%; n=34). After the diagnosis of SMF, median OS was 53.0 (18.2-87.8) months and leukemia-free survival at 4 years was 85.3%. According to the MYSEC-PM risk groups, the median OS in months was not reached for the low-risk group, 53.0 [HR 1.5 (0.2-15.2)], 33.8 [HR 2.2 (0.2-19.7)] and 12.1 [HR 7.5 (0.9 -64.2)] for the intermediate (int)-1, int-2 and high-risk groups, respectively (p=0.04). In the low-risk group, OS was 85.7% at 3 years. As for DIPSS, at 3 years, there was an OS of 100%, 49.5%, 66.7% and 0% for the low, int-1, int-2 and high-risk groups, respectively (p<0.001). The predictive prognostic power, assessed by the death event, was sufficient both by the MYSEC-PM and DIPSS, with an area under the curve of 0.726 versus 0.744. After reclassification of risk groups according to the MYSEC-PM, 15 (38.5%) patients were reclassified (12 upstaged and 3 under staged). Summary/Conclusion: The MYSEC-PM model demonstrated prognostic stratification capacity in the context of a real-life cohort, however without significant differences in the ability to predict OS, compared to DIPSS. There was also a significant percentage of patients understaged by DIPSS, which may imply more aggressive therapeutic strategies in young patients with good performance status. The validity of different prognostic models in the context of treatment is essential for their subsequent use in therapeutic decisions. Keywords: Prognosis, Myeloproliferative disorder, Myelofibrosis
PB2533: FREQUENCY, PATTERN, AND CLINICAL CORRELATES OF RENAL IRON ACCUMULATION IN THALASSEMIA MAJOR
Authors: Antonella Meloni, Luigi Barbuto, Laura Pistoia, Gianna Alberini, Antonella Cossu, Crocetta Argento, Domenico Maddaloni, Francesco Massei, Annamaria Carrà, Paola Maria Grazia Sanna, Vincenzo Positano, Filippo Cademartiri
Journal: HemaSphere (2023)

Topic: 27. Thalassemias Background: Iron overload is a common complication of thalassemia major (TM) which could result in organ damage and increased morbidity. Multiecho T2* Magnetic Resonance Imaging (MRI) is a well-established technique for cardiac and hepatic iron overload assessment, but there are very few report concerning the kidneys. Aims: The aim of this multicenter study was to evaluate frequency, pattern, and associations of renal iron accumulation in TM. Methods: Seventy-three beta-TM patients (35.65±10.17 years; 37 females) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) network were considered. Hepatic, cardiac, pancreatic, and renal iron overload was quantified by the gradient-echo T2* technique. In each kidney T2* was measured in anterior, posterolateral, and posteromedial parenchymal regions and the global T2* value was calculated as the average of the two kidneys T2* values. Results: T2* values in the right kidney were significantly lower than in the left kidney (41.61±10.34 ms vs. 44.41±9.51 ms, P<0.0001). The mean T2* value over the kidneys was 43.01±9.48 ms and a pathological value (<31 ms) was found in 9 (12.3%) patients. Global renal T2* values were not associated with age, gender, age at start of regular transfusions or chelation, and splenectomy. There was a significant negative correlation between serum ferritin levels and global renal T2* values (R=-0.359, P=0.002). Global renal T2* values showed a significant inverse correlation with MRI liver iron concentration (LIC) values (R=-0.425; P<0.0001) and a significant positive correlation with global pancreas T2* values (R=0.236; P=0.044), but were not associated with global heart T2* values. Global renal T2* values were not associated with serum creatinine levels or uric acid but showed a significant inverse correlation with serum lactate dehydrogenase (R=-0.458; P=0.002). Summary/Conclusion: Systemic T2* differences between left and right kidneys were found, with significant lower values in the right one. Kidney iron deposition was not very common in TM, but it was correlated with hemolysis and with hepatic and pancreatic iron deposition. Keywords: beta thalassemia, Iron overload, Magnetic resonance imaging
PB2538: FEASIBILITY AND SAFETY OF POWERPICC SOLO INSERTION THE SAPHENOUS VEIN IN CHILDREN WITH THALASSEMIA
Authors: Qin Ren, Fangfang Wu, Aihua Sun
Journal: HemaSphere (2023)

Topic: 27. Thalassemias Background: Hematopoietic stem cell transplantation is currently the only method to cure thalassemia. During the transplantation period the child needs to receive high doses of chemotherapy drugs, nutritional fluids and immunosuppressants, etc. A reasonable selection of intravenous devices ensures the safety and effectiveness of intravenous therapy for the child. The PowerPICC SOLO’s multi-channel design, thin-walled large lumen and high flow rate meet the characteristics of children who require multi-channel intravenous therapy during transplantation. Aims: To investigate the feasibility and safety of PowerPICC SOLO insertion the saphenous vein in children with thalassemia Methods: We reviewed 24 children admitted to the laminar flow room from June 2022 to December 2022 for upper limb PowerPICC SOLO placement and PowerPICC SOLO placement through the saphenous vein. 12 children with upper extremity PICC placement were used as the control group and 12 children with lower extremity PICC placement in the saphenous vein were used as the test group. The average length of placement, single puncture frequency, catheter ectasia and complications were compared between the two groups. Results: The mean placement time of the children in the test group was (32.7±0.16) minutes and the frequency of single puncture was (1.15±0.06), which was not statistically different from that of the upper limb PICC group. The differences were not uniformly significant compared with the upper limb PICC group. In terms of catheter ectasia and complications (venous thrombosis, phlebitis, catheter slippage) were lower than in the control group (P < 0.05). Summary/Conclusion: PICC placement via the saphenous vein can reduce the risk of catheter ectasia and complications, alleviate the child’s pain, and meet the child’s need for hematopoietic stem cell transplantation.It reduces the risk of catheter ectasia and complications, reduces the pain of the child, and meets the needs of the child for intravenous treatment during hematopoietic stem cell transplantation Keywords: Thalassemia
PB2694: EFFECT OF NARRATIVE NURSING ON ANXIETY, DEPRESSION AND STIGMA IN PATIENTS AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: Jie Tang, Jing Wen, Zhenglan He, Qin Ren, Fangfang Wu
Journal: HemaSphere (2023)

Topic: 35. Quality of life and palliative care Background: Allogeneic hematopoietic stem cell transplantation is an effective method for the treatment of hematological malignancies or non-malignant blood diseases. Hematopoietic stem cell transplantation provides patients with a chance of cure. However, patients need to receive large doses of radiotherapy during transplantation, which makes them less immune to disease after transplantation and even have almost zero white blood cells in the bone marrow vacuity stage. Therefore, local and systemic infections are easy to occur, resulting in increased psychological pressure of patients. Narrative nursing means that clinical nursing staff with narrative ability can absorb, explain and respond to patients’ stories and difficulties, and provide them with medical care full of respect, vitality and empathy. Nurses can fully understand and perceive patients’ pain experience and disease experience, make appropriate responses, and discover nursing points, so as to implement clinical nursing intervention for patients. Studies have shown that narrative nursing can alleviate negative emotions and reduce the level of stigma in patients.. Aims: To explore the effect of narrative nursing on anxiety, depression and stigma of patients after hematopoietic stem cell transplantation. Methods: A total of 100 patients who underwent hematopoietic stem cell transplantation in the hematology department of a first-class hospital in Chongqing from January 2022 to December 2022 were selected as subjects. They were randomly divided into observation group and control group. The control group received routine psychological guidance; Observation group was given narrative nursing on the basis of control group. General data questionnaire, general Hospital Anxiety and Depression Scale and Social Impact scale were used to evaluate the effects before and after intervention. Results: Before intervention, there was no statistical significance in anxiety, depression and stigma scores in 2 groups (P>0.05). After intervention and 1 month after intervention, anxiety and depression scores in observation group were lower than those in control group (P<0.05). The scores of social exclusion, economic discrimination, intrinsic shame and social isolation were also lower than those of the control group (P<0.05). Summary/Conclusion: Narrative nursing can relieve anxiety, depression and other negative emotions of patients after hematopoietic stem cell transplantation, and reduce the level of stigma. It is worthy of clinical application. Keywords: Depression, Hematopoietic cell transplantation
P1460: INDUCTION OF FETAL HEMOGLOBIN BY TARGETED DELETION OF ZINC FINGER DOMAIN WITHIN BCL11A GENE USING CRISPR-CAS9 TECHNOLOGY
Authors: Irfan Hussain, Kainaat Mumtaz, Fizza Iftikhar, Safana Farooq, Syed Muhammad, Areeb Ahmed, Dilawar Khan, Hammad Hassan, Oliver Ottmann, Afsar Mian
Journal: HemaSphere (2023)

Topic: 27. Thalassemias Background: The expression of β-like globin genes in humans is controlled during development, with fetal γ-globin genes replaced by adult β-globin genes after birth. Mutations in the β-globin gene can cause β-hemoglobinopathies such as sickle cell disease (SCD) and β-thalassemia. Elevated fetal hemoglobin (HbF) levels can mitigate the clinical severity of these diseases, and reactivating the expression of γ-globin genes is a promising treatment strategy. Disrupting the binding of the BCL11A transcriptional repressor complex to the γ-globin gene promoter provides a novel approach for inducing fetal hemoglobin. Aims: The clinical severity of SCD and β-thalassemia can be mitigated by elevated fetal hemoglobin (HbF) levels. Therefore, we aimed to induce the expression of γ-globin genes restart tge production of fetal hemoglobin by disrupting the binding of the BCL11A transcriptional repressor complex to the γ-globin gene promoter. Methods: Using in silico tools, molecular dynamics simulation, and homology modelling, the binding efficiency of zinc fingers (Znf) 4, 5, and 6 of BCL11A was predicted. CRISPR-Cas9 genome editing was used to delete Znf4 in K562 cell lines and adult mobilized CD34+ hematopoietic stem and progenitor cells (HSPCs). The effect of the deletion on γ-globin expression and survival was evaluated. Results: In comparison with the other zinc finger domains, deletion of Znf4 decreased the binding affinity of BCL11A by > 70-fold, resulting in a readily detectable increase in γ-globin expression with a preferential increase in G-gamma. Deletion of znf4 in mobilized CD34+ cells from patients with β-thalassemia major also results in an improved phenotype and likely a survival advantage for maturing erythroid cells after editing. Summary/Conclusion: Disrupting Znf4 of BCL11A or the TTGACCA motif can improve gene editing therapy strategies for β-hemoglobinopathies by disrupting the interaction between BCL11A and the γ-globin gene promoter. Our findings revealed that Znf4 is a suitable target for disrupting BCL11A-mediated hemoglobin switching and complete failure in protein-protein interactions with functional partners and the γ-globin gene promoter. Keywords: Hematopoietic stem cell, Hemoglobin, Thalassemia
PB2700: ANXIETY AND DEPRESSION IN HEMATOLOGICAL MALIGNANCIES PATIENTS: FOCUS ON TREATMENT ADHERENCE
Authors: Dmitry E Vybornykh, Eduard Gemdzhian, Tatyana Moiseeva, Tatiana Gaponova, Daria Novikova
Journal: HemaSphere (2023)

Topic: 35. Quality of life and palliative care Background: Treatment adherence is able to change significantly under the influence of mental disorders that affects the results of treatment. Aims: To study the effect of anxiety and depressive disorders on treatment adherence in patients with hematological malignancies (HM). Methods: The study included 117 patients: 51 men and 66 women, aged 19 to 67 years, with Hodgkin’s lymphoma (HL) - 88, acute lymphoblastic leukemia (ALL) - 16 and aplastic anemia (AA) - 13 patients. When examining patients, the Brief Psychiatric Rating Scale (BPRS) was used, as well as some psychometric methods. Results: Anxiety and depression were detected in 36 (40.9%) patients with HL, 8 (50%) with ALL and three (23.1%) in the AA group. It was found that the medium treatment adherence (51-76% likelihood of adherence to treatment recommendations as measured by Quantitative Treatment Adherence Scale (COP25)) was in 2/3 of patients, low (50% or less) and high (76% or more) - in the remaining 1/3 of patients. With medium and low adherence to treatment, the risk of developing adverse events increases by an average on 1.7 folded. Treatment adherence is significantly higher in patients of older age groups (over 45 years). Pessimism and disruption of social ties were negatively correlated (p =0.05 and p = 0.03 respectively) with treatment adherence. A significant positive correspondence with treatment adherence was found with the following types of attitudes towards the disease: anosognosic, hypochondriac and egocentric, and a significant negative correspondence with anxious, melancholic and dysphoric types of attitudes towards the disease. Summary/Conclusion: Anxiety and depression contribute to a decrease in the adherence of patients with HM to treatment. Correction of such psychopathological disorders and improvement of adherence should be carried out jointly by hematologists and mental health professionals. Keywords: Treatment, Depression, Hematological malignancy
PB2499: BLINATUMOMAB SEQUENTIAL ANTI-CD22 CAR-T CELLS AND HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR SUCCESSFUL TREATMENT OF B LYMPHOBLASTIC LEUKEMIA EXTRAMEDULLARY RECURRENCE: A CASE REPORT
Authors: Hao Yao, Shan Zhang, Xu-Pai Zhang, Dan Chen, Qian Zhang, Guang-Cui He, Fangyi Fan, Yi Su, Hai Yi
Journal: HemaSphere (2023)

Topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical Background: Extramedullary recurrence is an important cause of treatment failure in patients with B lymphoblastic leukemia(B-ALL). The recurrence is mainly observed in the central nervous system, while cutaneous lymph nodes are rare. Blinatumomab is a prescription medicine used to treat B-ALL in patients who still have detectable traces of cancer after chemotherapy. Chimeric antigen T(CAR-T) cells targeting CD22 has shown to be beneficial treatment effect on refractory/relapsed. Yet, few studies have reported data in the treatment of B-ALL extramedullary recurrence, especially in the skin, with blinatumomab sequential CAR-T cells. Aims: To investigate B-ALL patients with skin recurrence who received sequential allogeneic hematopoietic stem cell transplantation after blinatumomab and anti CD22 CAR-T cell therapy and achieved cytological remission. Methods: A patients with B-ALL who has extramedullary recurrence received sequential allogeneic hematopoietic stem cell transplantation after blinatumomab and anti CD22 CAR-T cell therapy were retrospectively analyzed. Results: The patient of B-ALL with skin recurrence who received sequential allogeneic hematopoietic stem cell transplantation after blinatumomab and anti CD22 CAR-T cell therapy and achieved cytological remission. A 51 old man with co-expression of CD19 and CD22, who used blinatumomab for three consecutive weeks before being transferred to our department. Skin biopsy and flow cytometry showed that CD19 (partially) and CD22 (dim+) were still expressed, which was considered to be involved in B-lymphoblastic lymphoma. After receiving anti-CD22 CAR-T cell therapy and sequential allogeneic hematopoietic stem cell transplantation, no abnormal B lineage primitive cells were found in bone marrow. Summary/Conclusion: Blinatumomab has a good clinical therapeutic effect on CD19 positive T cells in bone marrow, while it cannot remove the extramedullary recurrent leukemia cells which infiltrated in the skin. After sequential anti-CD22 CAR-T cell therapy and bridging hematopoietic stem cell transplantation, which can further remove leukemia cells and improving the patient’s outcome. Trial registration: ChicTr.org.cn number, ChiCTR2200059816, Registered 12 May 2022. Keywords: Allogeneic hematopoietic stem cell transplant, B cell acute lymphoblastic leukemia, CD19, CAR-T
PB1701: REPLACING THE CURRENT METHODS IN LEUKEMIA DIAGNOSTICS WITH OPTICAL GENOME MAPPING AND CAS9-DIRECTED NANOPORE SEQUENCING.
Authors: Sabrina Commandeur-Jan, Eva van den Berg- de Ruiter, Vincent Vroom, Arjen Scheper, Lennart Johansson, Laura Bosscher, Nettie Rietema, Gineke Drok, Birgit Sikkema-Raddatz, Nine Knoers, Cleo van Diemen, Eddy de Boer
Journal: HemaSphere (2023)

Topic: 1. Acute lymphoblastic leukemia - Biology & Translational Research Background: Leukemias are clinically and genetically heterogeneous and the type of genetic aberration(s) is important for progression prognosis and choice of treatment. Consequently, a high-throughput and comprehensive genetic diagnosis is needed. Due to the different types of aberrations, a combination of techniques (SNP-array, karyotyping and FISH) is needed for diagnosis and even then relevant abnormalities may go undetected because of resolution and other limitations of the different techniques. Aims: The current techniques are time-consuming, labor-intensive and as mentioned, may not detect all aberrations. Therefore, we want to test whether we can replace the current diagnostic workflow with optical genome mapping (OGM). Methods: Here we studied an unselected cohort of 18 bone marrow aspirates using routine diagnostics alongside OGM and tested if we were able to identify all previously reported aberrations. For additional aberrations, not verified using current methods, Cas9-directed guide RNAs were designed to perform long read (Nanopore) sequencing 1) to confirm these aberrations and 2) to define the precise breaking points of suspected deletions and duplications between 2 OGM labels. Results: All reported aberrations were identified with OGM and 12 additional aberrations with putative clinical relevance were detected. We could confirm 4/12 extra findings with current methods, whereas 8/12 could not be assessed due to a lack of resolution of these methods. We confirmed the remaining variants with Nanopore sequencing. Moreover, we showed the added value of redefining the breaking points, e.g., in 3 patients with suspected deletions in a 42 Kb region between 2 OGM labels on chromosome 17, including TP53. Using nanopore sequencing, the deletions were redefined to be 1.2 Kb deletions localized beside (and not including) TP53 and consequently had no clinical relevance. Summary/Conclusion: We showed that our diagnostic workflow can be replaced by OGM. Nanopore sequencing can be used for confirmation of variants and to redefine the breaking points when needed. Guide RNAs can be designed in advance because the low resolution OGM regions with clinical relevance are known, which allows confirmation within to 1 to 2 days. Keywords: Chromosomal abnormality, Cytogenetics
P1417: BASELINE CALCIUM WAS ASSOCIATED WITH PROGNOSIS AFTER CAR T-CELL THERAPY
Authors: Xindi Wang, Yu Hu, Heng Mei
Journal: HemaSphere (2023)

Topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical Background: CD19 chimeric antigen receptor (CAR) T-cell therapy has achieved remarkable efficacy in the field of treating relapsed/refractory B-cell malignancies. However, electrolyte disorders including hypoelectrolytemia during CAR T-cell therapy are also common events at incidences of 30-80% and connected to toxicity and prognosis. Aims: To investigate the relationship between electrolyte abnormalities and prognosis after CAR T-cell therapy. Methods: We retrospectively analyzed routine indicators in 71 patients with non-Hodgkin lymphoma and B-cell acute lymphoblastic leukemia (B-ALL) who received anti-CD19 CAR T-cell therapy. From baseline pre-lymphodepletion to 30 days after CAR T-cell infusion. Abnormalities of electrolytes were determined in accordance with Common Terminology Criteria for Adverse Events, version 4.03. Additionally, the assessment of cytokine release syndrome (CRS) and immune-effector cell-associated neurotoxicity syndrome (ICANS) was referred to the American Society for Transplantation and Cellular Therapy guidelines. The time from the CAR T-cell infusion to the date of disease progression, relapse, or death from any cause was considered progression-free survival (PFS), and the time from the infusion to the date of death from any cause was considered overall survival. In accordance with the 2014 Cheson criteria released, the lymphoma relapse or progression were assessed based on the CT scan or 18FDG-PET/CT results. According to NCCN guideline, minimal residual disease was used to assess leukemia relapse or progression. Results: This retrospective single-center study included 71 patients diagnosed with B-cell malignancies (NHL, n=45; B-ALL, n=26), with a median age of 45 years (range, 13–74) and 53.50% male. The incidences of hypokalemia, hypocalcemia, hypophosphatemia, hypomagnesemia, hypochloremia, and hyponatremia were, respectively, 84.51%, 83.10%, 76.06%, 73.24%, 57.75%, and 42.25%. In addition, 28.17% of patients had all six electrolyte abnormalities during treatment (Figure 1A). The electrolyte alterations were resulted from CRS independent of impaired renal function. The nadir values of electrolytes were also influenced by the severity of CRS (Figure 1B). Importantly, we found that low baseline calcium was associated with inferior PFS (P =0.003, Figure 1C) and poor response rate (P =0.016, Figure 1D), especially for patients with B-ALL (Figure 1E). Summary/Conclusion: CRS impacted the electrolyte levels independent of renal function. In addition, low baseline calcium was associated with inferior PFS and poor response rate.Keywords: Clinical outcome, Cellular therapy, Clinical data